The conduct of diagnostic and invasive therapeutic procedures in children often requires the use of sedation or anesthesia which can be coupled with adverse events. This is of particular importance when these children are enrolled in investigational protocols, when some of those diagnostic studies are obtained for research purpose, and when these children have rare diseases. Further, in some cases, little is known about the anesthetic implications of these diseases as little is known about the diseases themselves. At the NIH clinical center, we often face the challenge of anesthetizing children with rare diseases (mastocytosis, NOMID, Niemann-Pick, autosomic recessive polycystic kidney disease-congenital-hepatic fibrosis) for the conduct of diagnostic and novel therapeutic procedures. We aim to understand the anesthetic implications of these diseases, to determine the incidence of anesthesia-related adverse events, and to delineate the better anesthetics for each of these situations.